LAIR1 Human

LAIR-1 is characterized by the presence of immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in its cytoplasmic tail. These motifs are essential for delivering inhibitory signals to immune cells. The primary ligands for LAIR-1 are collagen and collagen domain-containing proteins, which are abundant in both circulation and tissues .

LAIR-1 is broadly expressed on various immune cells, including monocytes, dendritic cells (DCs), macrophages, and certain subsets of T cells . Its expression is tightly regulated to maintain immune homeostasis. For instance, LAIR-1 is highly expressed on intermediate monocytes and plasmacytoid DCs, and its expression can be upregulated during inflammatory conditions .

The primary function of LAIR-1 is to inhibit immune cell activation and prevent excessive immune responses. Upon engagement with its ligands, the ITIMs in LAIR-1 become phosphorylated, creating docking sites for phosphatases such as SHP-1 and SHP-2. These phosphatases dephosphorylate key molecules involved in activating receptor signaling pathways, thereby inhibiting cellular activation .

LAIR-1 plays a significant role in modulating the immune response during inflammation. It is upregulated on monocytes and DCs during the inflammatory phase and tends to restore its expression during the resolution phase . Additionally, LAIR-1 ligation on monocytes inhibits toll-like receptor (TLR)4 and interferon (IFN)-α-induced signals, highlighting its role as a negative regulator under inflammatory conditions .

Research on LAIR-1 has provided valuable insights into its regulatory functions and potential therapeutic applications. For example, targeting LAIR-1 could be a strategy to modulate immune responses in autoimmune diseases or to enhance immune tolerance in transplantation . Furthermore, understanding the differential expression of LAIR-1 during immune cell differentiation and activation can help in developing targeted therapies for various inflammatory and immune-mediated conditions .